It is known from the state of the art that it is possible to bring about photo-hyperpolarisation of the membrane potential, in particular of nerve cells. In particular the publications: Janovjak, Harald; Szobota, Stephanie; Wyart, Claire; Trauner, Dirk; Isacoff, Ehud Y (2010), “A light-gated, potassium-selective glutamate receptor for the optical inhibition of neuronal firing”. Nat. Neurosci. 13: 1027-1032 and WO 2010/051343 report hyperpolarisation of the membrane potential and inhibition of the electrical activity of a genetically modified neurone through the use of photosensitive proteins expressed in the cell through viral infection, which can be activated following a light-induced conformational change.
In addition to this the publications: Han, Xue; Boyden, Edward S. (2007) “Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution”. PloS One 2: e299 and US 2011/301,529 report hyperpolarisation of the membrane potential and inhibition of the electrical activity of a cell through the use of light-sensitive ion pumps of microbial original (microbial rhodopsin) expressed in the cell through viral infection.
Similar hyperpolarisation techniques have been used in the cure of degenerative diseases of the retina (Busskamp, Volker; Duebel, Jens; Balya, David; Fradot, Mathias; Viney, Tim J; Siegert, Sandra; Groner, Anna C; Cabuy, Erik; Forster, Valérie; Seeliger, Mathias; Biel, Martin; Humphries, Peter; Paques, Michel; Mohand-Said, Saddek; Trono, Didier; Deisseroth, Karl; Sahel, José A; Picaud, Serge; Roska, Botond (2010) Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science 329: 413-417; Polosukhina, Aleksandra; Litt, Jeffrey; Tochitsky, Ivan; Nemargut, Joseph; Sychev, Yivgeny; De Kouchkovsky, Ivan; Huang, Tracy; Borges, Katharine; Trauner, Dirk; Van Gelder, Russell N; Kramer, Richard H (2012) Photochemical restoration of visual responses in blind mice. Neurone. 2012 75(2):271-82) and focal epilepsy (Tønnesen, J., Sørensen, A. T., Deisseroth, K., Lundberg, C. & Kokaia, M. (2009) Optogenetic control of epileptiform activity. Proc. Natl. Acad. Sci. USA 106: 12162-12167. Paz, Jeanne T; Davidson, Thomas J; Frechette, Eric S; Delord, Bruno; Parada, Isabel; Peng, Kathy; Deisseroth, Karl; Huguenard, John R. (2013) Closed-loop optogenetic control of thalamus as a tool for interrupting seizures after cortical injury. Nat. Neurosci. 16: 64-70) exclusively in experimental animals.
These strategies presuppose genetic expression of light-sensitive heterologous proteins in the cell through viral constructs. At the present time it is still not possible to photoinhibit excitable cells without genetically modifying the target cells. These strategies have unavoidable collateral effects. In fact the viral vectors are potentially toxic, give rise to inflammatory reactions in the host tissue, and cause expression of a magnitude and duration which can vary over time. In addition to this the heterologous protein can interfere with cell functions and give rise to functional abnormalities.
It is known from previous publications by the inventors that a device comprising a glass substrate, an anode contact, a semiconductor polymer and electrolyte means is capable of giving rise to depolarisation of the membrane potential of excitable cells placed above the polymer surface. This depolarisation gives rise to photoexcitation similar to that which can be obtained through electrical stimulation [M. R. Antognazza, D. Ghezzi, D. Musitelli, M. Garbugli and G. Lanzani (2009) A hybrid solid-liquid polymer photodiode for the bioenvironment. Appl. Phys. Lett. 94: 243501; D. Ghezzi, M. R. Antognazza, M. Dal Maschio, E. Lanzarini, F. Benfenati and G. Lanzani (2011) A hybrid bioorganic interface for neuronal photoactivation. Nat. Commun. 2: 166; D. Ghezzi, M. R. Antognazza, R. Maccarone, S. Bellani, E. Lanzarini, N. Martino, M. Mete, G. Pertile, S. Bisti, G. Lanzani and F. Benfenati (2013) A polymer-based interface restores light sensitivity in rat blind retinas. Nat. Phot. 7: 400-406].
The inventors have surprisingly found that by layering a photo-sensitive polymer directly onto a substrate of non-conducting material a device is obtained which produces a potential difference across the contact surface with the cell, when subjected to a pulse of light radiation, such as to induce hyperpolarisation of the membrane of the excitable cell, thus obtaining an effect which is the opposite of that in the known device.